Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.

International audienceVezatin is an integral membrane protein associated with cell-cell adhesion complex and actin cytoskeleton. It is expressed in the developing and mature mammalian brain, but its neuronal function is unknown. Here, we show that Vezatin localizes in spines in mature mouse hippocampal neurons and codistributes with PSD95, a major scaffolding protein of the excitatory postsynaptic density. Forebrain-specific conditional ablation of Vezatin induced anxiety-like behavior and impaired cued fear-conditioning memory response. Vezatin knock-down in cultured hippocampal neurons and Vezatin conditional knock-out in mice led to a significantly increased proportion of stubby spines and a reduced proportion of mature dendritic spines. PSD95 remained tethered to presynaptic terminals in Vezatin-deficient hippocampal neurons, suggesting that the reduced expression of Vezatin does not compromise the maintenance of synaptic connections. Accordingly, neither the amplitude nor the frequency of miniature EPSCs was affected in Vezatin-deficient hippocampal neurons. However, the AMPA/NMDA ratio of evoked EPSCs was reduced, suggesting impaired functional maturation of excitatory synapses. These results suggest a role of Vezatin in dendritic spine morphogenesis and functional synaptic maturation

A new mouse model for the trisomy of the Abcg1-U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

Mental retardation in Down syndrome (DS), the most frequent trisomy in humans, varies from moderate to severe. Several studies both in human and based on mouse models identified some regions of human chromosome 21 (Hsa21) as linked to cognitive deficits. However, other intervals such as the telomeric region of Hsa21 may contribute to the DS phenotype but their role has not yet been investigated in detail. Here we show that the trisomy of the 12 genes, found in the 0.59 Mb (Abcg1-U2af1) Hsa21 sub-telomeric region, in mice (Ts1Yah) produced defects in novel object recognition, open-field and Y-maze tests, similar to other DS models, but induces an improvement of the hippocampal-dependent spatial memory in the Morris water maze along with enhanced and longer lasting long-term potentiation in vivo in the hippocampus. Overall, we demonstrate the contribution of the Abcg1-U2af1 genetic region to cognitive defect in working and short-term recognition memory in DS models. Increase in copy number of the Abcg1-U2af1 interval leads to an unexpected gain of cognitive function in spatial learning. Expression analysis pinpoints several genes, such as Ndufv3, Wdr4, Pknox1 and Cbs, as candidates whose overexpression in the hippocampus might facilitate learning and memory in Ts1Yah mice. Our work unravels the complexity of combinatorial genetic code modulating different aspect of mental retardation in DS patients. It establishes definitely the contribution of the Abcg1-U2af1 orthologous region to the DS etiology and suggests new modulatory pathways for learning and memor

Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase

The cystathionine β-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological processes.Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line.We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS

A new mouse model for the trisomy of the Abcg1–U2af1 region reveals the complexity of the combinatorial genetic code of down syndrome

Mental retardation in Down syndrome (DS), the most frequent trisomy in humans, varies from moderate to severe. Several studies both in human and based on mouse models identified some regions of human chromosome 21 (Hsa21) as linked to cognitive deficits. However, other intervals such as the telomeric region of Hsa21 may contribute to the DS phenotype but their role has not yet been investigated in detail. Here we show that the trisomy of the 12 genes, found in the 0.59 Mb (Abcg1–U2af1) Hsa21 sub-telomeric region, in mice (Ts1Yah) produced defects in novel object recognition, open-field and Y-maze tests, similar to other DS models, but induces an improvement of the hippocampal-dependent spatial memory in the Morris water maze along with enhanced and longer lasting long-term potentiation in vivo in the hippocampus. Overall, we demonstrate the contribution of the Abcg1–U2af1 genetic region to cognitive defect in working and short-term recognition memory in DS models. Increase in copy number of the Abcg1–U2af1 interval leads to an unexpected gain of cognitive function in spatial learning. Expression analysis pinpoints several genes, such as Ndufv3, Wdr4, Pknox1 and Cbs, as candidates whose overexpression in the hippocampus might facilitate learning and memory in Ts1Yah mice. Our work unravels the complexity of combinatorial genetic code modulating different aspect of mental retardation in DS patients. It establishes definitely the contribution of the Abcg1–U2af1 orthologous region to the DS etiology and suggests new modulatory pathways for learning and memory

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have positive effects on learning and memory capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is also known to be a convulsant drug at higher dose and DS persons are more prone to epileptic seizures than the general population. This raises concerns over what long-term effects of treatment might be in the DS population. The cause of increased propensity for epilepsy in the DS population and which Hsa21 gene(s) are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB, coding for the cystein protease inhibitor cystatin B, is involved in progressive myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the effect of an increase in Cstb gene dosage on spontaneous epileptic activity and susceptibility to PTZ-induced seizure. To this end we generated a new mouse model trisomic for Cstb by homologous recombination. We verified that increasing copy number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of the gene in the brain, we checked transgenic animals for presence of locomotor activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic epilepsy and we tested if those animals were prone to PTZ-induced seizure. Overall, the results of the analysis shows that an increase in Cstb does not induce any spontaneous epileptic activity and neither increase or decrease the propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage should not interfere with PTZ-treatment

Les astres et le destin. Astrologie et divination en Asie orientale

L’enseignement théorique et pratique de l’astrologie et de la divination constitue une tradition transmise depuis l’antiquité. Il forme un excellent domaine de recherche sur l’enseignement d’une science traditionnelle. Les civilisations de l’Inde et de l’Asie Orientale, par la variété de leurs langues et écritures comme par l’intensité de leurs croisements culturels, offrent un terrain d’investigation particulièrement riche. Les articles rassemblés ici visent à donner une vue globale des deux facettes de la transmission des techniques divinatoires : tradition et innovation. Alors que l’on ne tient compte d’ordinaire, en matière d’astrologie et d’arts divinatoires que d’une seule aire culturelle, ce numéro aborde à la fois la Chine et les cultures sinisées que sont la Corée, le Japon et le Viêtnam, l’Inde et le Cambodge indianisé, le Tibet, héritier de l’Inde, et la Mongolie, largement dépendante du Tibet culturellement. Cette diversification des angles permet de mettre en évidence de multiples transferts culturels : le Cambodge indianisé reprend des traditions calendériques chinoises, tout comme le Tibet, tandis que la Mongolie se forge une identité à partir des éléments qu’il reçoit du Tibet et de la Chine, sur la base de concepts propres plus anciens. On découvre l’usage politique de la divination, notamment par la fondation d’institutions officielles, ainsi que les surprenantes stratégies d’adaptation des arts divinatoires à l’époque moderne, que ce soit par le déguisement scientifique ou par le retour à l’identité nationale

Optical capture system for Real-time convection PCR instrument

本實驗在即時熱對流核酸擴增儀 (Real-time convection PCR instrument) 中，設計大收光量光信號截取系統，以同時讀取系統當中八個毛細管中兩種螢光特性。先以光學模擬軟體ZEMAX來模擬成像系統，本系統N.A值為0.19，收光量可提升至10倍 。成像品質上，系統之徑向能量累積 (Radial energy distribution, RED) 分佈均在74%以上，調變轉換函數(Modulation transfer function, MTF)在100 lp/mm均為0.8以上，且中心鏡組與邊緣鏡組之光通量差異為10%，實際測量差為7%。另一方面測量濃度0.45μM的Fluorescein的螢光訊號，且總螢光強度約為背景值之10倍，系統的收光量也比直接收光大約10倍。In this study Real-time convection PCR instrument, the design of a large amount of light received the optical signal of the intercepted system to read eight of the capillary system of two fluorescent properties. First of all, using ZEMAX optical software to simulate the imaging system, the system received 0.19 of N.A, the flux can be increased to 10 times. Image quality, the system of Radial energy distribution is 74%. Modulation transfer function at 100 lp / mm is 0.8, the center with the edge of the flux difference are 10%, the actual measured difference is 7%. Actually, measuring the concentration of 0.45μM of Fluorescein signal, and the total fluorescence intensity is about 10 times of the background value, The system of the flux is higher 10 times than directly received light.第一章 緒論............................1 1.1 序言...............................1 1.2 聚合酶連鎖反應.....................2 1.3熱對流式聚合酶連鎖反應..............5 1.4 即時聚合酶連鎖反應.................7 第二章 光學系統設計...................10 2.1 光通量............................10 2.2 光學系統設計......................11 2.3 成像品質評估函數..................12 第三章 成像鏡組設計...................17 3.1 物鏡設計..........................17 3.2 轉向透鏡設計......................18 3.3 兩片式鏡..........................19 3.4 兩片式物鏡與轉向透鏡整體結構 .....20 3.5 三片式鏡..........................25 3.6 三片式物鏡與轉向透鏡整體結構.......26 3.7三片式物鏡與轉向透鏡結構之模擬討論..33 第四章 實體架設........................34 4.1實體公差分析........................34 4.2實體結構............................36 4.3轉向透鏡測試........................37 4.4螢光檢測............................38 第五章 總結............................40 參考附錄...............................41 圖目錄 頁次 圖1 聚合酶連鎖反應之三階段..................4 圖2 聚合酶連鎖反之DNA複製的數量級...........5 圖3 Rayleigh-Be′nard convection cell......5 圖4 Convective PCR in a Rayleigh–B′enard cell ..6 圖5 層形熱對流PCR..................................7 圖6 環形熱對流.....................................7 圖7螢光強度........................................8 圖8 Taqman probe method .........................9 圖9 光通量比較圖..................................10 圖10光學讀取系統設計..............................12 圖11三種單色像差..................................13 圖12 RED示意圖....................................14 圖13點擴散函數....................................15 圖14經光學系統後之測試條紋........................16 圖15條紋測試標準..................................16 圖16 MTF定義比較圖...............................16 圖17 MTF曲線 ....................................16 圖18 MTF曲線 ....................................16 圖19平行光顯微物鏡................................17 圖20 轉向透鏡之功用...............................18 圖21物鏡一片鏡組 .................................19 圖22物鏡一片光斑圖................................19 圖23物鏡兩片......................................19 圖24 物鏡兩片光斑圖...............................19 圖25 兩片式物鏡與轉向透鏡整體結構 ................20 圖26 兩片式物鏡轉向透鏡 F200. ....................21 圖27 兩片式物鏡轉向透鏡F200反轉...................21 圖28兩片式物鏡轉向透鏡F200雙凸....................22 圖29 兩片式整體成像品質..........................23 圖30兩片式整體模擬討論............................24 圖31三片式物鏡 ...................................25 圖32 三片式物鏡MTF圖 ....................................25 圖33三片式物鏡RED ...........................25 圖34 三片式物鏡與轉向透鏡整體結構 .................26 圖35三片式物鏡與轉向透鏡F200球面......................27 圖36三片式物鏡之像散............................27 圖37球面與非球面透鏡 ..........................28 圖38三片式物鏡 轉向透鏡F200非球面 ............29 圖39三片式物鏡轉向透鏡非球面之整體成像品質...........30 圖40式物鏡 轉向透鏡F400X2模擬討論.......................31 圖41三片式物鏡與轉向透鏡F400x2之整體成像品質.............32 圖42三片式物鏡轉向透鏡整體模擬討論 ....................33 圖43鏡片距離對焦距、成像品質影響 ....................34 圖44模擬實際系統放大率驗算...............................35 圖45系統放大率...................................35 圖46CCD成像面.................................35 圖47實際測試 .......................36 圖48未加轉向透鏡F400X2前...............................37 圖49加轉向透鏡F400x2後.............................37 圖50 螢光檢測 Ι.................................38 圖51螢光檢測 ΙΙ 軟體轉換..........................3

Analysis of PTZ-induced tonico-clonic seizure in 2n, Ts and Tt mice.

<p>The number of PTZ-treated mice, the number of convulsing mice and the percentage of convulsing mice are given for each genotype and PTZ dose.</p

Generation of a tandem duplication of the <i>Cstb</i> gene on Mmu10.

<p>The targeting vector containing a loxP site (green arrow), a selectable antibiotic resistance gene (neo), and the 5′part of the <i>Hprt</i> gene were integrated in the <i>Cstb</i> locus (<i>Cstbtm1Yah</i>), leading to the tandem duplication of <i>Cstb</i>. The <i>Cstb</i> allele was checked by Southern analysis with probes A and B, and BstXI restriction enzyme, showing a fragment of 9.6 kb for the wild-type allele (wt) and a 11.6 kb fragment (probe A) or a 13.2 kb fragment (probe B) for the <i>Cstb</i> (T) allele.</p

Evaluation of susceptibility of 2n, Ts and Tt mice to PTZ-induced seizure.

<p>(a) Dose-response curves showing the ratio of the number of convulsing mice observed (obs) or predicted (pred) to the total number of injected animals for each PTZ dose. (b) Distributions of latencies of seizure for each genotype at the different doses of PTZ administered. (c) Global survival curves of 2n (blue), Ts (red) and Tt (green) mice (probability of seizure according to time, latencies right censored at 1800 sec).</p